Activation of the parasympathetic nervous system is necessary for normal meal-induced insulin secretion in rhesus macaques

David A. D'Alessio, Timothy J. Kieffer, Gerald J. Taborsky, Peter J Havel

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Meal-induced insulin secretion is thought to be regulated primarily by absorbed nutrients and incretin hormones released from the gastrointestinal tract. In addition, the parasympathetic nervous system (PNS) is known to mediate preabsorptive, or cephalic phase, insulin secretion. Despite evidence that the PNS remains activated during the absorptive phase of the meal, its role in mediating postprandial insulin secretion has not been established. To study the role of the PNS in absorptive phase insulin release, we measured plasma concentrations of glucose as well as islet hormones and incretins in six healthy rhesus monkeys before and for 60 min after meals while they were infused with saline (control), atropine (muscarinic blockade), or trimethaphan (nicotinic blockade). During the infusion of saline, plasma levels of glucose, pancreatic polypeptide (PP), insulin, glucose-dependent insulinotropic polypeptide, and glucagon-like peptide-1 increased promptly after meal ingestion and remained elevated throughout the 60 min of the study. The PP response was nearly abolished in animals treated with trimethaphan, indicating functional blockade of PNS input to the islet, and in contrast to the control study, there were minimal changes in plasma concentrations of glucose, incretin hormones, and insulin. Because trimethaphan inhibited glycemic and incretin stimuli in addition to blocking PNS input to the islet, it was not possible to discern the relative roles of these factors in the stimulation of insulin secretion. Atropine also significantly decreased PNS transmission to the islet, as reflected by PP levels similar to those observed with trimethaphan. Unlike the trimethaphan study, plasma glucose levels rose normally during atropine treatment and were similar to those in the control study over the course of the experiments (114 ± 22 and 132 ± 23 mmol/L·60 min, respectively). In addition, the rise in plasma glucagon-like peptide-1 following the meal was not suppressed by atropine, and the glucose-dependent insulinotropic polypeptide responses were only modestly decreased. Despite the significant increases in circulating glucose and incretins, plasma insulin levels were greatly attenuated by atropine, so that the 60 min responses were more comparable to those during trimethaphan treatment than to those in the control study (atropine, 3,576 ± 1,284; trimethaphan, 4,128 ± 2,616; control, 15,834 ± 5,586 pmol/L·60 min; P < 0.05). Thus, muscarinic blockade markedly suppressed the meal-induced insulin response despite normal postprandial glycemia and significant elevations of incretins. These results indicate that activation of the PNS during the absorptive phase of meals contributes significantly to the postprandial insulin secretory response.

Original languageEnglish (US)
Pages (from-to)1253-1259
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume86
Issue number3
DOIs
StatePublished - 2001

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Parasympathetic Nervous System
Neurology
Trimethaphan
Macaca mulatta
Meals
Incretins
Chemical activation
Insulin
Atropine
Glucose
Plasmas
Pancreatic Polypeptide
Glucagon-Like Peptide 1
Hormones
Cholinergic Agents
Peptides
Polypeptides
Nutrients
Gastrointestinal Tract
Animals

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Activation of the parasympathetic nervous system is necessary for normal meal-induced insulin secretion in rhesus macaques. / D'Alessio, David A.; Kieffer, Timothy J.; Taborsky, Gerald J.; Havel, Peter J.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 86, No. 3, 2001, p. 1253-1259.

Research output: Contribution to journalArticle

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